Neuroscientists and other experts in the field have long held that regenerating the cells and tissues of the central nervous system (CNS) following a neurological injury was not possible. However, recent research has confirmed that certain cellular and molecular compounds, as well as tissue conduits, may be used to improve functional recovery after onset of a neurodegenerative disorder, such as Alzheimer's disease (AD), stroke, Parkinson's disease (PD), multiple sclerosis (MS), spinal cord injuries (SCI), and traumatic brain injuries (TBI).
Alzheimer's disease is a chronic, degenerative and terminal neurological disorder with a number of factors influencing its development and manifestations. About 5.4 million Americans and 36 million worldwide suffer from Alzheimer's, a number which is expected to increase dramatically. Every 68 seconds a new individual develops Alzheimer's in the USA only. An average Alzheimer's patient spends $2,400/year on therapeutics. Direct and indirect costs of Alzheimer's and other dementias in the USA are more than $170 billion and $400 billion worldwide annually. Thus, developing a drug that reverses the pathology of Alzheimer's will significantly reduce these costs.
Minor pathological changes may appear in patients decades before clinical symptoms of Alzheimer's disease occur, and they may be found in middle-aged and elderly persons without obvious symptoms of AD. The preclinical stage of Alzheimer's disease (i.e., preclinical Alzheimer's disease) is characterized by mild impairment in verbal memory, which probably reflects damage to the hippocampus, with later involvement of areas governing language, spatial orientation, attention, concentration, and psychomotor speed. See Skoog (2000) N. Eng. J. Med. 343:502-503, incorporated herein by reference.
Several animal and human efficacy studies have confirmed that therapeutics including macromolecules and even stem cells can reach the brain and upper spinal cord through the roof of the nose directly, without having to access the blood stream or pass through the blood brain barrier (BBB) as they travel along the olfactory and trigeminal pathways and nerve fibers. Human studies have indicated that intranasally delivered insulin decreases the cognitive decline associated with Alzheimer's. Experts in the field have highlighted ten different mechanisms through which intranasal insulin significantly enhances cognition in AD and other neurodegenerative diseases, including reduction in amyloid plaque synthesis with enhanced breakdown, elevation of acetylcholine brain levels, enhanced neurogenesis and synaptogenesis, increased glucose uptake by brain cells with enhanced oxidative phosphorylation and energy metabolism. See, for example, Dhamoon et al. (2009) “Intranasal insulin improves cognition and modulates beta-amyloid in early AD” Neurology 72(3):292-3; Reger et al. (2008) “Intranasal insulin improves cognition and modulates beta-amyloid in early AD” Neurology 70(6):440-8; Craft (2007) “Insulin resistance and Alzheimer's disease pathogenesis: potential mechanisms and implications for treatment” Curr. Alzheimer Res. 4(2):147-52; Grossi et al. (2009) “Clioquinol decreases amyloid-beta burden and reduces working memory impairment in a transgenic mouse model of Alzheimer's disease” J. Alzheimers Dis. 17(2):423-40; and Hanson et al. (2008) “Intranasal delivery bypasses the blood-brain barrier to target therapeutic agents to the central nervous system and treat neurodegenerative disease” BMC Neurosci. 10; 9 Suppl 3:S5., each of which is incorporated herein by reference.
Although therapies for Alzheimer's disease and other neurodegenerative disorders exist, additional treatment options are needed. For instance, currently-approved Alzheimer's drugs are symptomatic and may be used for 24 months at most; they are not effective and cannot slow down or reverse the disease.